Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

Positive correlations between plasma BPI level and MPO-DNA and S100A8/A9 in myocardial infarction.

Bactericidal/permeability-increasing protein (BPI) exhibits a number of important characteristics. RNA-seq analysis revealed that the BPI expression was increased in platelets of (non)ST-elevated myocardial infarction (NSTEMI/STEMI) patients. Activated platelets can induce NETosis which may be accompanied by the release of myeloperoxidase-DNA (MPO-DNA) and S100A8/A9. This study investigated the plasma BPI levels in myocardial infarction patients and its correlation with MPO-DNA and S100A8/A9. This prospective study recruited 80 control individuals, as well as 63 NSTEMI and 59 STEMI patients who were admitted to the First Affiliated Hospital of Bengbu Medical College for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) between May 1, 2020 and August 31, 2020. Demographic and clinical characteristics, clinical indicators, hs-CRP, IL-1ß, MPO-DNA (a circulated marker of NETs), circulating levels of S100A8/A9 and BPI were measured from each individual. The severity of coronary lesions was evaluated by the Gensini score, based on the results of the CAG. Pearson's or spearman's correlation was used to examine the correlation between BPI and the above-mentioned parameters, as well as the severity of coronary artery disease. Linear regression analysis was applied to identify the independent predictive factors of BPI. Received operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma BPI for MI. The plasma BPI levels increased by 8.76 times in the STEMI group and 5.38 times in the NSTEMI group compared to the control group. The plasma level of hs-CRP and IL-1ß in both STEMI and NSTEMI groups were also significantly higher than the control group. In addition, the plasma levels of MPO-DNA and S100A8/A9 in the STEMI and NSTEMI groups were significantly higher than the control group. Plasma levels of BPI were positively correlated with IL-1ß, hs-CRP, MPO-DNA and S100A8/A9. The correlation between BPI and the severity of coronary artery disease was also significant. The optimal cutoff value of plasma BPI was 35.1705 ng/ml for MI patients from the ROC curve analysis. Plasma BPI levels are increased in myocardial infarction patients and positively correlated with MPO-DNA and S100A8/A9. Plasma BPI level may serve as a potential biomarker of myocardial infarction.

Elevated Uric Acid Levels Promote Vascular Smooth Muscle Cells (VSMC) Proliferation via an Nod-Like Receptor Protein 3 (NLRP3)-Inflammasome-Dependent Mechanism.

BACKGROUND Hyperuricemia has a pathogenic role in the development of hypertension and other cardiovascular diseases (CVD). Uric acid has been reported to activate Nod-like receptor protein 3 (NLRP3)-inflammasome and alter vascular smooth muscle cells (VSMC). However, the potential mechanisms underlying this association are still not understood. The aim of this study was to investigate the role and potential mechanisms of uric acid in proliferation of VSMC. MATERIAL AND METHODS Cell Counting Kit-8 (CCK-8) proliferation assay and colony formation assay were performed to determine the proliferative ability of VSMC under uric acid stimulation. Immunofluorescence microscopy was carried out to determine the expression of Alpha-smooth muscle actin (alpha-SMA). In addition, real-time PCR and Western blot were used to detect the expression of NLRP3-inflammasome, and ELISA was performed to measure the levels of IL-18 and IL-1ß. RESULTS The results showed that uric acid increases the proliferation of VSMC and induces alpha-SMA accumulation. We also found that uric acid increases the level of NLRP3 and induces NLRP3-inflammasome activation. The expressions of uric acid-induced inflammatory markers IL-1ß and IL-18 were decreased by the inhibitor MCC950. CONCLUSIONS Our findings revealed that uric acid induces inflammation through NLRP3-inflammasome-mediated VSMC proliferation. NLRP3 may be a new therapeutic target for hypertension.